Clinical Eligibility Criteria Research Articles

Abstract 6455: Investigating clinical trial eligibility criteria to improve MatchMiner trial matching

Abstract As the number of precision medicine (PM) trials and the volume of patient genomic data have grown, it has become challenging for clinicians and trial staff to identify PM trial options for patients. At Dana-Farber Cancer Institute (DFCI), we have addressed this challenge by developing our own open source institutional trial matching software called MatchMiner. MatchMiner algorithmically matches patient genomic and clinical data with PM trial eligibility data. PM trial eligibility data is manually curated into a human- and computer-readable structured format called clinical trial markup language (CTML), for trial matching with DFCI’s institutional genomic assay OncoPanel. MatchMiner has 2 main modes of clinical use: (1) patient-centric, where clinicians can search for trial matches for individual patients and (2) trial-centric, where trial staff can identify patients that match their trial’s genomic eligibility. Thus far, more than 300 DFCI patients have enrolled onto trials facilitated by MatchMiner. In its current implementation, MatchMiner uses limited clinical data (gender, age, and cancer type) to match patients to trials. Although this limited data gives clinicians a head start on assessing available trial options, incorporating more clinical data into MatchMiner would provide more precise trials options and reduce additional work to assess patient eligibility. Here, we investigated clinical trial eligibility criteria that were available for trials at DFCI with the goal of improving specificity of trial matching for MatchMiner. We attempted to answer 2 main research questions 1) what categories of clinical data comprise the eligibility criteria for precision medicine trials at DFCI and 2) which categories are most relevant for trial matching? We first investigated the clinical eligibility criteria across several PM lung cancer trials. After extracting the inclusion and exclusion criteria from the protocol documents, we found criteria could be classified into 10 distinct categories. The most common categories making up almost half of the eligibility criteria were “Prior Therapy” and “Prior or Concurrent Non-Cancerous Disease”. Within some categories, we found it appropriate to also make subcategories to make our analysis more informative such as “Prior Therapy, Surgery” or “Disease Status, CNS”. We next broadened our search to non-lung trials to see if criteria was consistent across other cancer types. We found similar proportions of clinical criteria for the non-lung trials compared to the lung trials, but did find some additional subcategories. Overall, having similar categories of criteria across trials suggests that common clinical data could be used for many different PM trials. Currently, we are investigating which categories are most relevant for trial matching and the use of AI for structuring unstructured clinical data. Citation Format: Harry Klein, Tali Mazor, Matthew Galvin, Jason Hansel, Emily Mallaber, Pavel Trukhanov, James Provencher, James Lindsay, Michael Hassett, Ethan Cerami. Investigating clinical trial eligibility criteria to improve MatchMiner trial matching [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6455.

Abstract 380: Prehospital Ground and Helicopter-Based Extracorporeal Cardiopulmonary Resuscitation (ECPR) Reduce Barriers to ECPR: A GIS Model

Introduction: Evidence suggests that ECPR can improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). However, over 50% of potential ECPR candidates are unable to qualify in the current hospital-based system due to geographic limitations. This study employs a Geographic Information System (GIS) model to estimate the number of ECPR eligible patients within the U.S. in the current hospital-based system, a prehospital ECPR ground-based system, and a prehospital ECPR HEMS-based system (Figure 1). Methods: We constructed a GIS model to estimate ground and helicopter transport times. Time-dependent rates of ECPR eligibility were derived from the Resuscitation Outcome Consortium (ROC) database, while the Cardiac Arrest Registry to Enhance Survival (CARES) registry determined the number of OHCA patients meeting ECPR criteria within designated transportation times. EMS response time, ECPR candidacy determination time, and on-scene time were modeled based on data from the EROCA trial (Figure 1). The combined model was used to estimate the total ECPR candidates in each system. Results: The CARES registry recorded 736,066 OHCA patients from 2013 to 2021. After applying clinical eligibility criteria, 24,661 (3.4%) patients were eligible for ECPR. When considering overall ECPR eligibility within 45 minutes from OHCA to initiation, only 11.76% of clinically eligible patients qualified in the current hospital-based system. The prehospital ECPR HEMS-based system exhibited a four-fold increase in ECPR eligibility (49.3%), while the prehospital ground-based system showed a more than two-fold increase (28.4%). Conclusions: The study demonstrates a two-fold increase in ECPR eligibility for a field-deployable ground-based system and a four-fold increase for a prehospital ECPR HEMS-based system compared to the current hospital-based OHCA system. This novel GIS model can inform future ECPR implementation strategies, optimizing systems of care.

Comparing stroke rehabilitation inpatients and clinical trials eligibility criteria: A secondary chart review analysis revealing that most patients could have been excluded from rehabilitation trials based on comorbidity status

Background The generalizability of treatments examined in rehabilitation randomized controls trials (RCTs) partly depend on the similarity between trial subjects and a stroke rehabilitation inpatient population. The aim of this study was to determine the proportion of stroke rehabilitation inpatients that would have been eligible or ineligible to participate in published stroke RCTs. Methods This was a secondary analysis of chart review data collected as part of an independent quality improvement initiative. Data pertaining to the characteristics of stroke rehabilitation inpatients (e.g. age, cognitive impairment, previous stroke, comorbidities) were extracted from the medical charts of patients consecutively admitted to an inpatient stroke rehabilitation unit at a large urban rehabilitation hospital in Canada. Using the exclusion criteria categories of stroke RCTs identified from a systematic scoping review of 428 RCTs, we identified how many stroke rehabilitation inpatients would have been eligible or ineligible to participate in stroke RCTs based on their age, cognitive impairment, previous stroke and presence of comorbidities. Results In total, 110 stroke rehabilitation inpatients were included. Twenty-four percent of patients were 80 years of age or older, 84.5% had queries or concerns regarding patient cognitive abilities, 28.0% had a previous stroke, and 31.8% had a severe stroke. Stroke rehabilitation inpatients had six comorbidities on average. Based on these factors, most stroke rehabilitation inpatients could have been excluded from stroke RCTs, with cognitive impairment the most common RCT exclusion criteria. Conclusions Changes to the design of RCTs would support the development of clinical practice guidelines that reflect stroke rehabilitation inpatient characteristics, enhancing equity, diversity, and inclusion within samples and the generalizability of results.

Effect of probiotic supplementation on wound healing in postoperative patients

Background: Delayed wound healing, particularly in chronic wounds, is a significant global public health issue. The World Health Organization (WHO) reports that over 6 million people in the United States experience delayed wound healing annually, resulting in a healthcare cost of $25 billion USD. Probiotics, known for their anti-inflammatory properties, have potential in influencing skin immunity by facilitating the transfer of cytokines and immune cells from Peyer's patches to the skin. Nevertheless, the precise impact of probiotics on postoperative wound healing remains an area with limited research.
 Objective: Determine the effectiveness of probiotic supplements in wound healing in patients with surgical wounds
 Method: Literature search is done by advanced searching on Pubmed, Cochrane, Scopus, and EBSCOhost with eligibility criteria determined by the author.
 Results: There were three articles relevant to clinical questions and eligibility criteria that had been established, consisting of one systematic review article from the randomized controlled trial (RCT) study and two RCT articles. The SR/MA article includes good-quality RCT studies. The SR/MA article showed insignificant results on the effect of probiotic administration on healing. The RCT article showed significant results on the effect of probiotics on surgical wound healing, but the confidence level was low in one of the articles.
 Conclusion: Probiotic supplementation on wound healing in postoperative patients is not conclusive. This can be affected by the type of probiotic strain, dosage, duration of administration, and location of the surgical wound.

Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer

BackgroundAdjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information.MethodsWe performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A–subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years.ResultsOf 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1).ConclusionsAmong women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.)

Anatomic suitability for transapical transcatheter mitral valve implantation using a tether-based device.

Transcatheter mitral valve implantation (TMVI) is a novel therapeutic option for treating symptomatic mitral valve disease. Evaluating patient anatomical suitability is a critical step in the TMVI screening process, but currently requires specialized software and computerized device models. This analysis sought to assess the effectiveness of simple and standardized multislice computed tomography (MSCT) anatomic measurements for their ability to discriminate between patients who passed anatomical screening for Tendyne™ TMVI. Subjects screened for the Tendyne Expanded Clinical Study from January 2016 through September 2019 were included. Core laboratory screening measurements included mitral annular (MA) dimensions at end-systole and end-diastole, simulated device implantation, and neo-left ventricular outflow tract (LVOT) area. Additionally, nine standard measurements of patient anatomy were assessed for their predictive value of patients passing the anatomic screening process. Out of 496 subjects screened for eligibility, 257 subjects met clinical eligibility criteria with MA dimensions within the manufacturer's suggested range: 153 (59.5%) underwent TMVI while 104 (40.5%) were excluded from the study for other anatomic reasons (76% due to risk of LVOT obstruction). CT-derived left ventricular end-systole diameter (LVESD) had the highest discriminatory power for predicting TMVI anatomical suitability (area under the curve of 0.908, p < 0.0001). The mitral inter-commissural (IC) dimension was best predictive of annular dimensions being within range, with dimensions <30 or >50 mm resulting in a negative predictive value of 94.4%. MSCT-derived mitral IC dimension and LVESD easily performed measures that are effective predictors of anatomical suitability or screen failure for this tether-based TMVI device.

Validation of the prognostic value of a three-gene signature and clinical parameters-based risk score in prostate cancer patients.

The study aimed to validate the prognostic value of the Prostatype® risk score (P-score), which includes a three-gene signature and conventional risk factors, in a retrospective cohort. All 716 patients diagnosed with prostate cancer from 2008 to 2010 at Skåne University Hospital, Sweden, were included. After excluding patients based on pathological and clinical eligibility criteria, RNA quality, and presence of metastases at diagnosis, a final cohort comprising 316 patients was further analyzed. Expression levels of three genes (IGFBP3, F3, and VGLL3) were measured in archived formalin-fixed paraffin-embedded core needle biopsies. The gene expression data were combined with clinical parameters (Gleason score, prostate-specific antigen, and clinical tumor stage) to calculate the P-score for each patient. Predictive performance of the P-score in terms of prostate cancer-specific mortality (PCSM), distant metastasis and adverse pathological outcomes were investigated. The P-score predicted both PCSM (hazard ratio [HR] = 1.6) and metastasis (HR = 1.46). The P-score had an area under curve (AUC) of 0.93 when predicting the PCSM risk at 10 years (95% confidence interval [CI]: 0.89-0.98), which was significantly better than both D'Amico (AUC: 0.81, 95% CI: 0.72-0.90, p < 0.001) and UCSF-CAPRA (AUC: 0.88, 95% CI: 0.80-0.96, p < 0.05). Decision curve analysis showed a higher net benefit of the P-score compared to both D'Amico and CAPRA. All three risk scores performed similarly in the prediction of distant metastases. For patients who underwent radical prostatectomy (RP), a higher P-score correlated with adverse pathological features such as pathologic tumor stage T3-4 (p < 0.0001) and ≥International Society of Urological Pathology grade group 3 (p < 0.0001). Our findings provide evidence for the prognostic value of the P-score. The P-score predicted the risk for PCSM more accurately than the D'Amico and CAPRA scores. Performance was similar when predicting the risk for development of distant metastases within 10 years. Moreover, the P-score correlated with adverse pathological outcomes in RP specimens. Thus, the P-score could provide useful information for patients and their doctors to make informed decisions at the time of diagnosis.

TESLA Trial: Rationale, Protocol, and Design

Background Mechanical thrombectomy has been shown to be effective in patients with acute ischemic stroke secondary to large‐vessel occlusion and small to moderate infarct volume. However, there are no randomized clinical trials for large‐core infarct volume comparing mechanical thrombectomy to medical therapy in the population selected based solely on noncontrast computed tomography brain scan. The TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke) randomized clinical trial is designed to address this clinical question. Methods The TESLA trial aim is to demonstrate the efficacy (3‐month and 1‐year disability following stroke) and safety of intraarterial mechanical thrombectomy in patients with large‐volume infarction assessed with a noncontrast computed tomography scan. The TESLA trial design is a prospective, randomized controlled, multicenter, open‐label, assessor‐blinded anterior circulation acute ischemic stroke trial with adaptive enrichment design, enrolling up to 300 patients. Patients with anterior circulation large‐vessel occlusion who meet the imaging and clinical eligibility criteria with a large‐core infarction on the basis of noncontrast computed tomography Alberta Stroke Program Early CT Score (2–5) adjudicated by a site investigator will be randomized in a 1:1 ratio to undergo intraarterial thrombectomy or best medical management up to 24 hours from last known well. Results The primary efficacy outcome is utility‐weighted modified Rankin Scale (mRS) score distribution at 90 days between the groups. The results will be based on an intention‐to‐treat analysis that will examine the Bayesian posterior probability that, adjusted for Alberta Stroke Program Early CT Score, patients with large‐core infarct volume treated with intra‐arterial thrombectomy have higher expected utility‐weighted mRS than those treated with best medical management alone. The primary safety outcome is the 90‐day death rate. Key secondary outcomes are dichotomized mRS 0 to 2 and 0 to 3 outcomes, ordinal mRS scores, and quality of life (EuroQol 5 Dimension 5 Level survey) at 90 days and 1 year, utility‐weighted mRS at 1 year, hemicraniectomy rate, and rate of 24‐hour symptomatic intracranial hemorrhage in both groups. Conclusion TESLA is a pragmatic trial, designed to address the unanswered question of the efficacy and safety of intra‐arterial thrombectomy in patients with large infarcts diagnosed by the site investigator only on noncontrast computed tomography scan secondary to anterior circulation large‐vessel occlusion up to 24 hours from stroke symptoms onset.

A data-driven approach to optimizing clinical study eligibility criteria

ObjectiveFeasible, safe, and inclusive eligibility criteria are crucial to successful clinical research recruitment. Existing expert-centered methods for eligibility criteria selection may not be representative of real-world populations. This paper presents a novel model called OPTEC (OPTimal Eligibility Criteria) based on the Multiple Attribute Decision Making method boosted by an efficient greedy algorithm. MethodsIt systematically identifies the optimal criteria combination for a given medical condition with the optimal tradeoff among feasibility, patient safety, and cohort diversity. The model offers flexibility in attribute configurations and generalizability to various clinical domains. The model was evaluated on two clinical domains (i.e., Alzheimer's disease and Neoplasm of pancreas) using two datasets (i.e., MIMIC-III dataset and NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC) database). ResultsWe simulated the process of automatically optimizing eligibility criteria according to user-specified prioritization preferences and generated recommendations based on the top-ranked criteria combination accordingly (top 0.41–2.75%) with OPTEC. Harnessing the power of the model, we designed an interactive criteria recommendation system and conducted a case study with an experienced clinical researcher using the think-aloud protocol. ConclusionsThe results demonstrated that OPTEC could be used to recommend feasible eligibility criteria combinations, and to provide actionable recommendations for clinical study designers to construct a feasible, safe, and diverse cohort definition during early study design.

Preclinical Evaluation of 89Zr-Panitumumab for Biology-Guided Radiation Therapy

Biology-guided radiation therapy (BgRT) uses real-time line-of-response data from on-board positron emission tomography (PET) detectors to guide beamlet delivery during therapeutic radiation. The current workflow requires 18F-fluorodeoxyglucose (FDG) administration daily before each treatment fraction. However, there are advantages to reducing the number of tracer injections by using a PET tracer with a longer decay time. In this context, we investigated 89Zr-panitumumab (89Zr-Pan), an antibody PET tracer with a half-life of 78 hours that can be imaged for up to 9 days using PET. The BgRT workflow was evaluated preclinically in mouse colorectal cancer xenografts (HCT116) using small-animal positron emission tomography/computed tomography (PET/CT) for imaging and image-guided kilovoltage conformal irradiation for therapy. Mice (n=5 per group) received 7 MBq of 89Zr-Pan as a single dose 2 weeks after tumor induction, with or without fractionated radiation therapy (RT; 6×6.6Gy) to the tumor region. The mice were imaged longitudinally to assess the kinetics of the tracer over 9 days. PET images were then analyzed to determine the stability of the PET signal in irradiated tumors over time. Mice in the treatment group experienced complete tumor regression, whereas those in the control group were killed because of tumor burden. PET imaging of 89Zr-Pan showed well-delineated tumors with minimal background in both groups. On day 9 postinjection, tumor uptake of 89Zr-Pan was 7.2 ± 1.7 in the control group versus 5.2 ± 0.5 in the treatment group (mean percentage of injected dose per gram of tissue [%ID/g] ± SD; P=.07), both significantly higher than FDG uptake (1.1 ± 0.5 %ID/g) 1 hour postinjection. To assess BgRT feasibility, the clinical eligibility criteria was computed using human-equivalent uptake values that were extrapolated from preclinical PET data. Based on this semiquantitative analysis, BgRT may be feasible for 5 consecutive days after a single 740-MBq injection of 89Zr-Pan. This study indicates the potential of long-lived antibody-based PET tracers for guiding clinical BgRT.

Implementing High Intensity Home-Based Rehabilitation Following Stroke: A Descriptive Study

<h3>Research Objectives</h3> To describe the implementation of a novel high intensity home-based rehabilitation (HIHR) program for a subgroup of patients with stroke. <h3>Design</h3> A descriptive study of the adoption of HIHR, including observed process measures and patient outcomes. <h3>Setting</h3> One hospital and homecare agency. <h3>Participants</h3> Clinical eligibility criteria for HIHR are: ischemic or hemorrhagic stroke, NIH Stroke Scale score ≤10, AM-PAC 6-Clicks mobility score 17-22, readmission risk ≤35%, and a subjectively determined level of appropriate caregiver support at home. We included records for patients discharged to HIHR October 2021 through February 2022. <h3>Interventions</h3> Primary interventions for HIHR include (1) identification of eligible patients in the hospital; (2) high frequency of physical, occupational, and/or speech therapy at home over a shorter episode relative to traditional homecare; and (3) a weekly interdisciplinary care coordination meeting. <h3>Main Outcome Measures</h3> Adoption was measured as the number discharged to HIHR relative to the number eligible. Process measures were episode length and the number of completed therapy visits. The primary patient outcome was functional status at HIHR discharge according to the mobility subsection score of the Continuity Assessment Record and Evaluation (CARE) tool, which ranges 15 (low function) to 90 (high function). <h3>Results</h3> Of 94 eligible patients, 26 (27.7%) discharged to HIHR. Other eligible patients discharged primarily to an inpatient rehabilitation facility (23.4%) or traditional homecare (21.3%). The median (IQR) length of HIHR episodes was 20.5 (17-27) days. Median visit counts by discipline were 4 (2-5) for occupational therapy, 6 (3-7) for physical therapy, and 4 (0-7) for speech therapy. The median CARE mobility score at HIHR discharge was 80 (51-88). <h3>Conclusions</h3> High intensity home-based rehabilitation can be implemented for a subgroup of patients with stroke. Patients had acceptable functional outcomes. The relatively low adoption we observed indicates an opportunity to refine HIHR inclusion criteria and/or to address gaps in hospital discharge planning communication. Future research should compare HIHR to traditional post-acute care and enable optimal matching of therapy service intensity in HIHR to patients' specific rehabilitation needs. <h3>Author(s) Disclosures</h3> No conflicts of interest.

Factors Associated With Receiving Longer Than Recommended Therapy Among Culture-Negative Pulmonary Tuberculosis Patients.

US tuberculosis (TB) guidelines recommend treatment ≥6 months with a regimen composed of multiple effective anti-TB drugs. Since 2003, a 4-month regimen for a specific subset of TB patients has also been recommended. We used 2011-2018 US National Tuberculosis Surveillance System data to characterize factors associated with 4-month (111-140 days) therapy among adult patients who had completed treatment and were potentially eligible at that time for 4-month therapy (culture-negative pulmonary-only TB, absence of certain risk factors, and initial treatment that included pyrazinamide). We used modified Poisson regression with backward elimination of main effect variables to calculate adjusted relative risks (aRRs). During 2011-2018, 63 393 adults completed TB treatment: 5560 (8.8%) were potentially eligible for 4-month therapy; of these, 5560 patients (79%) received >4-month therapy (median, 193 days or ∼6 months). Patients with cavitary disease were more likely to receive >4-month therapy (aRR, 1.10; 95% CI, 1.07-1.14) vs patients without cavitary disease. Patients more likely to receive 4-month therapy included patients treated by health departments vs private providers only (aRR, 0.94; 95% CI, 0.91-0.98), those in the South and West vs the Midwest, non-US-born persons (aRR, 0.95; 95% CI, 0.91-0.99) vs US-born persons, and aged 25-64 years vs 15-24 years. Most patients potentially eligible for 4-month therapy were treated with standard 6-month courses. Beyond clinical eligibility criteria, other patient- and program-related factors might be more critical determinants of treatment duration.

Abstract 270: Eligibility Of Out-of-hospital Cardiac Arrest Patients For Extracorporeal Cardiopulmonary Resuscitation In The United States: A Geographic Information System Model

Introduction: Recent evidence suggest that ECPR may improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). Eligibility criteria for ECPR are often based on patient age, clinical variables, and facility capabilities. Expanding access to ECPR across the U.S. requires a better understanding of how these factors interact with transport time to ECPR centers. Methods: We constructed a Geographic Information System (GIS) model to estimate the number of ECPR candidates in the U.S. We utilized a Resuscitation Outcome Consortium (ROC) database to model time-dependent rates of ECPR eligibility and the Cardiac Arrest Registry to Enhance Survival (CARES) registry to determine the total number of OHCA patients who meet pre-specified ECPR criteria within designated transportation times. Potential ECPR centers were categorized as Extracorporeal Membrane Oxygenation (ECMO)-ready, ECMO-capable, or percutaneous coronary intervention (PCI)-capable centers using data from the Extracorporeal Life Support Organization and the American Hospital Directory. The combined model was used to estimate the total ECPR candidates and the effects of patient and hospital factors on ECPR eligibility. Results: There were 588,203 OHCA patients in the CARES registry from 2013 to 2020. After applying clinical eligibility criteria, 22,104 (3.76%) OHCA patients were eligible for ECPR. The rate of ROSC increased with longer resuscitation time, which resulted in fewer ECPR candidates. The proportion of OHCA patients eligible for ECPR increased with older age cutoffs. Only 1.68% (9,889/588,203) of OHCA patients in the U.S. were eligible for ECPR based on a 45-minute transportation time to an ECMO-ready center model, representing the current state of ECPR in the U.S. The proportion of OHCA patients eligible for ECPR ranged from 0.68% (4,027 patients in the 15-minute transportation time to ECMO-ready center model) to 2.81% (16,558 patients in the 45-minute transportation time to PCI-capable center model). Conclusions: Less than 2% of OHCA patients are eligible for ECPR in the U.S. GIS models can identify the impact of clinical criteria, transportation time, and hospital capabilities on ECPR eligibility to inform future implementation strategies.

MatchMiner: an open-source platform for cancer precision medicine

Widespread, comprehensive sequencing of patient tumors has facilitated the usage of precision medicine (PM) drugs to target specific genomic alterations. Therapeutic clinical trials are necessary to test new PM drugs to advance precision medicine, however, the abundance of patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to PM trials. To facilitate enrollment onto PM trials, we developed MatchMiner, an open-source platform to computationally match genomically profiled cancer patients to PM trials. Here, we describe MatchMiner’s capabilities, outline its deployment at Dana-Farber Cancer Institute (DFCI), and characterize its impact on PM trial enrollment. MatchMiner’s primary goals are to facilitate PM trial options for all patients and accelerate trial enrollment onto PM trials. MatchMiner can help clinicians find trial options for an individual patient or provide trial teams with candidate patients matching their trial’s eligibility criteria. From March 2016 through March 2021, we curated 354 PM trials containing a broad range of genomic and clinical eligibility criteria and MatchMiner facilitated 166 trial consents (MatchMiner consents, MMC) for 159 patients. To quantify MatchMiner’s impact on trial consent, we measured time from genomic sequencing report date to trial consent date for the 166 MMC compared to trial consents not facilitated by MatchMiner (non-MMC). We found MMC consented to trials 55 days (22%) earlier than non-MMC. MatchMiner has enabled our clinicians to match patients to PM trials and accelerated the trial enrollment process.

Associations between insurance status and the cancer clinical trial enrollment process.

85 Background: Most patients with cancer experience multi-leveled barriers to clinical trial participation, potentially including financial concerns due to the complexity surrounding trial-related insurance coverage. Our study sought to understand the association between insurance status and cancer clinical trial eligibility, offer, and enrollment. Methods: This retrospective cohort study included patients with breast or ovarian cancer receiving a therapeutic cancer drug at the University of Alabama at Birmingham between January 2017 and February 2020. Available clinical trials and eligibility criteria were abstracted from OnCore and ClinicalTrials.gov. Patient trial eligibility, offer from provider, demographics, and clinical characteristics were abstracted from electronic medical records. Patient trial enrollment was determined via OnCore. Odds of clinical trial eligibility, offer, and enrollment by insurance status (private, public [Medicaid, Medicare]) were estimated using logistic regression models. Models estimating odds of trial offer and enrollment contained only eligible patients. Models were adjusted for patient age at diagnosis, race and ethnicity, rural-urban residence, Area Deprivation Index, cancer type, and cancer stage (early, late). Results: A total of 513 patients with breast (71%) or ovarian (29%) cancer were included in our analyses. Median age at diagnosis was 60 (interquartile range: 49-67) years; the majority were White (69%) and had early stage cancer (65%). Half of patients had private insurance (54%), and 46% of patients had public insurance (38% Medicare, 8% Medicaid). Patients with private insurance more often had early stage cancer compared to patients with public insurance (73% vs 57%). Almost two-thirds of patients (65%) were eligible for clinical trial enrollment. Of eligible patients (n = 333), 68% were offered a trial and 47% enrolled onto a trial. In adjusted analyses, patients with public vs private insurance had similar odds of clinical trial eligibility (odds ratio [OR] 0.95, 95% confidence intervals [CI] 0.61-1.48), being offered to participate (OR 1.23, 95% CI 0.71-2.14), and clinical trial enrollment (OR 1.13, 95% CI 0.68-1.89). Conclusions: Our results suggest oncologists do not assess trial eligibility or offering a trial based on insurance status, and patients do not differentially participate based on their insurance coverage. Further research is needed to understand implications of trial participation (e.g., out-of-pocket and time costs) for patients covered by differing insurance.

Eligibility of out-of-hospital cardiac arrest patients for extracorporeal cardiopulmonary resuscitation in the United States: A geographic information system model

BackgroundRecent evidence suggest that extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). Eligibility criteria for ECPR are often based on patient age, clinical variables, and facility capabilities. Expanding access to ECPR across the U.S. requires a better understanding of how these factors interact with transport time to ECPR centers. MethodsWe constructed a Geographic Information System (GIS) model to estimate the number of ECPR candidates in the U.S. We utilized a Resuscitation Outcome Consortium (ROC) database to model time-dependent rates of ECPR eligibility and the Cardiac Arrest Registry to Enhance Survival (CARES) registry to determine the total number of OHCA patients who meet pre-specified ECPR criteria within designated transportation times. The combined model was used to estimate the total number of ECPR candidates. ResultsThere were 588,203 OHCA patients in the CARES registry from 2013 to 2020. After applying clinical eligibility criteria, 22,104 (3.76%) OHCA patients were deemed eligible for ECPR. The rate of ROSC increased with longer resuscitation time, which resulted in fewer ECPR candidates. The proportion of OHCA patients eligible for ECPR increased with older age cutoffs. Only 1.68% (9,889/588,203) of OHCA patients in the U.S. were eligible for ECPR based on a 45-minute transportation time to an ECMO-ready center model. ConclusionsLess than 2% of OHCA patients are eligible for ECPR in the U.S. GIS models can identify the impact of clinical criteria, transportation time, and hospital capabilities on ECPR eligibility to inform future implementation strategies.

Barriers for cancer clinical trial enrollment: A qualitative study of the perspectives of healthcare providers

BackgroundBarriers to clinical trial enrollment have been the subject of extensive research; however, the rate of clinical trial participation has not improved significantly over time. Studies often emphasize patient-related barriers, but institutional and organizational barriers in the health care system may have a more substantial impact on clinical trial participation. ObjectiveTo qualitatively identify perceived barriers to clinical trial participation based on perspectives from healthcare providers. DesignQualitative research design with a phenomenological approach was used. A purposive sample of 18 healthcare providers participated in an in-depth focus group session. Participants were involved in cancer care and clinical research from a large hospital in the United States Midwest region. Data were transcribed, coded, and systematically analyzed through thematic content analysis. ResultsThe data revealed four levels of barriers to clinical trial enrollment, with emergent themes within each level: patient (beliefs or trust, distance to trial sites, health insurance coverage, language, and immigration status), provider (limited awareness of trial, time constraint, and non-cooperation from colleagues), clinical (eligibility criteria and clinical design), and institutional (policy and limited logistic support). ConclusionHealthcare providers face complex, multifaceted, and interrelated barriers to clinical trial enrollment. To overcome these barriers, health care organizations need to commit more human and financial resources, break down boundaries for more efficient inter-departmental cooperation, develop more coordinated efforts in promoting trial awareness and participation, and remove unnecessary regulatory barriers.

Uptake of community- versus clinic-based antiretroviral therapy dispensing in the Central Chronic Medication Dispensing and Distribution program in South Africa.

IntroductionSouth Africa's government‐led Central Chronic Medication Dispensing and Distribution (CCMDD) program offers people living with HIV the option to collect antiretroviral therapy at their choice of community‐ or clinic‐based pick‐up points intended to increase convenience and decongest clinics. To understand CCMDD pick‐up point use among people living with HIV, we evaluated factors associated with uptake of a community‐ versus clinic‐based pick‐up point at CCMDD enrolment.MethodsWe collected baseline data from October 2018 to March 2020 on adults (≥18 years) who met CCMDD clinical eligibility criteria (non‐pregnant, on antiretroviral therapy for ≥1 year and virologically suppressed) as part of an observational cohort in seven public clinics in KwaZulu‐Natal. We identified factors associated with community‐based pick‐up point uptake and fit a multivariable logistic regression model, including age, gender, employment status, self‐perceived barriers to care, self‐efficacy, HIV‐related discrimination, and perceived benefits and challenges of CCMDD.Results and DiscussionAmong 1521 participants, 67% were females, with median age 36 years (IQR 30–44). Uptake of a community‐based pick‐up point was associated with younger age (aOR 1.18 per 10‐year decrease, 95% CI 1.05–1.33), being employed ≥40 hours per week (aOR 1.42, 95% CI 1.10–1.83) versus being unemployed, no self‐perceived barriers to care (aOR 1.42, 95% CI 1.09–1.86) and scoring between 36 and 39 (aOR 1.44, 95% CI 1.03–2.01) or 40 (aOR 1.91, 95% CI 1.39–2.63) versus 10–35 on the self‐efficacy scale, where higher scores indicate greater self‐efficacy. Additional factors included more convenient pick‐up point location (aOR 2.32, 95% CI 1.77–3.04) or hours (aOR 5.09, 95% CI 3.71–6.98) as perceived benefits of CCMDD, and lack of in‐clinic follow‐up after a missed collection date as a perceived challenge of CCMDD (aOR 4.37, 95% CI 2.30–8.31).ConclusionsUptake of community‐based pick‐up was associated with younger age, full‐time employment, and systemic and structural factors of living with HIV (no self‐perceived barriers to care and high self‐efficacy), as well as perceptions of CCMDD (convenient pick‐up point location and hours, lack of in‐clinic follow‐up). Strategies to facilitate community‐based pick‐up point uptake should be tailored to patients’ age, employment, self‐perceived barriers to care and self‐efficacy to maximize the impact of CCMDD in decongesting clinics.

Augmenting Real-World Data Through Modeling Key Clinical Trial Eligibility Criteria: An Example of Patients With Non-small-Cell Lung Cancer Treated With Pembrolizumab.

To compare and characterize baseline characteristics and overall survival (OS) differences by key oncology eligibility criteria for real-world patients from the Flatiron Health database with advanced non-small-cell lung cancer (NSCLC) who received pembrolizumab monotherapy. Real world data (RWD) were from the Flatiron Health advanced NSCLC database and include patients who initiated pembrolizumab monotherapy (first, second, or third line of therapy) by November 30, 2019. At the data cutoff (May 31, 2020), the median survival follow-up time was 8.4 months. Eligible patients satisfy the criteria of Eastern Cooperative Oncology Group performance status of 0/1 and laboratory values indicative of adequate organ function. RWD were analyzed for all patients and patients with a programmed cell death ligand-1 tumor proportion score ≥ 1%. Patients were divided into three categories: ineligible, eligible, and unknown (who satisfy all observed criteria, with at least one missing). An augmented population was also formed, which combines the latter two groups through a propensity-based adjustment. At the data cutoff, N = 3,877 patients with NSCLC received pembrolizumab monotherapy (1L = 2,682, 2L = 946, and 3L = 249). OS was consistently lower for the ineligible with similar survival for the eligible and augmented. Among all patients, the median OS in months (95% CI) was 8.2 (7.5 to 9.6), 16.3 (14.5 to 18.4), 16.4 (15.1 to 19.3), and 16.8 (15.6 to 18.5) for the ineligible (47%, n = 1,827), unknown (27%, n = 1,045), eligible (26%, n = 1,005), and augmented, respectively. The results were similar for patients with a programmed cell death ligand-1 tumor proportion score ≥ 1%. Real-world patients who received pembrolizumab monotherapy and meet key clinical eligibility criteria exhibited similar baseline characteristics and OS profiles as the unknown and augmented patient groups. Population augmentation is a feasible approach for improving the power of RWD analysis.

Clinical Prioritization of Antispike Monoclonal Antibody Treatment of Mild to Moderate COVID-19

Clinical Prioritization of Antispike Monoclonal Antibody Treatment of Mild to Moderate COVID-19